Substance abuse is estimated to cost the nation over $180 billion annually (French et al., 2008; Harwood, 2004; Mark et al., 2007; Schori, 2011), yet little is known about whether current evidence-based preventive interventions (EBPI) can efficiently reduce these costs (i.e., whether program benefits are greater than the cost of operating the program; Aos et al., 2004, 2011; Heckman et al., 2010). This is largely because researchers lack three components vital to conducting high-quality benefit-costs analyses (BCAs) that reliably estimate the efficiency of substance abuse (SA) prevention efforts (Bukoski et al., 1998; Crowley et al., 2011e; Karoly, 2011; O'Connell et al., 2009). These include a lack of (1) cost estimates that account for the resources needed to adopt, implement and sustain SA prevention programs, (2) estimates of the social benefits gained from reducing SA risk factors in monetary terms, and (3) guidance around best practices and research priorities for evaluating SA prevention costs and benefits. To strengthen BCA practice, the research strategy described in this proposal will estimate and model the systemic costs of a large-scale NIDA-funded SA prevention effort, estimate the societal value of targeting specific SA risk factors, and identify best practices and research priorities for BCAs of SA prevention. Further, this work will provide the foundation for a productive research program as I transition to an independent investigator.